International Regulatory Collaboration on the Analysis of Nitrosamines in Metformin-Containing Medicines.
International regulatory laboratories
NDMA
drug supply
metformin
nitrosamines
Journal
The AAPS journal
ISSN: 1550-7416
Titre abrégé: AAPS J
Pays: United States
ID NLM: 101223209
Informations de publication
Date de publication:
21 04 2022
21 04 2022
Historique:
received:
18
01
2022
accepted:
24
03
2022
entrez:
22
4
2022
pubmed:
23
4
2022
medline:
26
4
2022
Statut:
epublish
Résumé
Recalls of some batches of metformin have occurred due to the detection of N-nitrosodimethylamine (NDMA) in amounts above the acceptable intake (AI) of 96 ng per day. Prior to the recalls, an international regulatory laboratory network had been monitoring drugs for nitrosamine impurities with each laboratory independently developing and validating multiple analytical procedures to detect and measure nitrosamines in metformin drugs used in their jurisdictions. Here, we provide an overview of the analysis of metformin active pharmaceutical ingredients (APIs) and drug products with 1090 samples (875 finished dosage forms (FDFs) and 215 API samples) tested beginning in November of 2019 through July of 2020. Samples were obtained internationally by a variety of approaches, including purchased, received from firms via information requests or selected by regional regulatory authorities (either at wholesalers or during GMP inspections). Only one nitrosamine (NDMA) was detected and was only present in some batches of metformin products. For API samples, 213 out of 215 lots tested had no measurable level of NDMA. For FDF samples tested, the number of batches with NDMA above the AI amount for patient safety was 17.8% (156/875). Based on these data, although the presence of NDMA was of concern, 82.2% of the samples of metformin drug products tested met quality and safety standards for patients. Regulatory agencies continue to collaborate extensively and work with marketing authorization holders to understand root causes of nitrosamine formation and agree on corrective actions to mitigate the presence of NDMA in future metformin batches.
Identifiants
pubmed: 35449372
doi: 10.1208/s12248-022-00702-4
pii: 10.1208/s12248-022-00702-4
doi:
Substances chimiques
Nitrosamines
0
Metformin
9100L32L2N
Dimethylnitrosamine
M43H21IO8R
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
56Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
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